Rotavirus (RV) causes severe dehydrating diarrhea in young children and moderate intestinal distress in adults (Greenberg et al., Gastroenterol. 136:1939, 2009). Analogously, RV infection of adult mice does not result in watery diarrhea but, rather, serves as a well-defined model of intestinal viral infection in which infectivity can be monitored by measuring levels of viral antigen shed in feces (Feng et al., Adv. Exp. Med. Biol. 412:233, 1997). RV predominantly infects and replicates in epithelial cells lining the small intestine (Sen et al., J. Virol. 83:10322, 2009). Bacterial flagellin, the primary component of bacterial flagella, directly and potently activates host defense gene expression in intestinal epithelial cells (IEC) (Zeng et al., J. Immunol. 171:3668, 2003) and, moreover, has been suggested to be a major target of innate and adaptive immunity in the intestine (Vijay-Kumar and Gewirtz, Mucosal Immunol. 2:197, 2009). The specific pattern of gene expression induced by flagellin in IEC can be viewed as an NF-κB-mediated transcriptional response highly reminiscent of that induced by bacterial pathogens such as Salmonella species and differs strikingly from that induced by RV, its components, or the viral dsRNA mimetic poly-(I:C), which induces a type I interferon-mediated antiviral response (Frias et al., Mucosal Immunol. 3:622, 2010; Vijay-Kumar et al., J. Immunol. 174:6322, 2005). Such flagellin-induced gene expression confers both IEC and mice with resistance to a variety of challenges including bacteria, chemicals, and radiation (Jones et al., Gut 60:748, 2011; Burdelya et al., Science 320:226, 2008; Jarchum et al., Infect. Immun. 79:1498, 2011; and Kinnebrew et al., J. Infect. Dis. 201:534, 2010). Moreover, and although flagellin does not induce expression of genes recognized to have antiviral activity, administration of flagellin reduced susceptibility of mice to a culture-adapted strain of RV (Vijay-Kumar et al., J. Immunol. 180:8280, 2008).